Corosolic acid reduces A549 and PC9 cell proliferation, invasion, and chemoresistance in NSCLC via inducing mitochondrial and liposomal oxidative stress

Corosolic acid is a pentacyclic triterpenoid isolated from Lagerstroemia speciosa, which is known to inhibit cancer cell proliferations. Whereas, the role of this compound on non-small cell lung cancer (NSCLC) cells still largely unclear. So, the aim of this study was to reveal the regulatory mechan...

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Autores principales:	Mingming Jin, Yue Wu, Yuqing Lou, Xiyu Liu, Yitian Dai, Wenxiao Yang, Congbiao Liu, Gang Huang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Corosolic acid Non-small cell lung cancer Oxidative stress Apoptosis Chemoresistance Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/50182fa5884445a1b56942f4fac6cc46
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spelling	oai:doaj.org-article:50182fa5884445a1b56942f4fac6cc462021-11-14T04:29:33ZCorosolic acid reduces A549 and PC9 cell proliferation, invasion, and chemoresistance in NSCLC via inducing mitochondrial and liposomal oxidative stress0753-332210.1016/j.biopha.2021.112313https://doaj.org/article/50182fa5884445a1b56942f4fac6cc462021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221010970https://doaj.org/toc/0753-3322Corosolic acid is a pentacyclic triterpenoid isolated from Lagerstroemia speciosa, which is known to inhibit cancer cell proliferations. Whereas, the role of this compound on non-small cell lung cancer (NSCLC) cells still largely unclear. So, the aim of this study was to reveal the regulatory mechanism of corosolic acid to NSCLC. Here, we cultured A549 and PC9 cells in increasing corosolic acid concentrations, as well as treated mice with a physiologically relevant concentration of the compound, and used metabolomics analysis and high-throughput sequencing to examine its influences on cell invasion and proliferation, chemoresistance, and metastasis. We found that corosolic acid inhibited cell invasion and proliferation in vivo and in vitro, as well as increase the chemosensitivity of both cell types to cisplatin. Furthermore, we found that corosolic acid destabilized the glutathione peroxidase 2-mediated redox system, which increased mitochondrial and liposomal oxidative stress. Corosolic acid also decreased the targeting protein for TPX2 level, which inhibited PI3K/AKT signaling and induced apoptosis. In addition, the accumulation of reactive oxygen species dissociated the CCNB1/CDK1 complex and induced G2/M cell cycle arrest. Taken collectively, the data indicate that corosolic acid reduces NSCLC cell invasion and proliferation, as well as chemoresistance, by inducing mitochondrial and liposomal oxidative stress.Mingming JinYue WuYuqing LouXiyu LiuYitian DaiWenxiao YangCongbiao LiuGang HuangElsevierarticleCorosolic acidNon-small cell lung cancerOxidative stressApoptosisChemoresistanceTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 144, Iss , Pp 112313- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Corosolic acid Non-small cell lung cancer Oxidative stress Apoptosis Chemoresistance Therapeutics. Pharmacology RM1-950
spellingShingle	Corosolic acid Non-small cell lung cancer Oxidative stress Apoptosis Chemoresistance Therapeutics. Pharmacology RM1-950 Mingming Jin Yue Wu Yuqing Lou Xiyu Liu Yitian Dai Wenxiao Yang Congbiao Liu Gang Huang Corosolic acid reduces A549 and PC9 cell proliferation, invasion, and chemoresistance in NSCLC via inducing mitochondrial and liposomal oxidative stress
description	Corosolic acid is a pentacyclic triterpenoid isolated from Lagerstroemia speciosa, which is known to inhibit cancer cell proliferations. Whereas, the role of this compound on non-small cell lung cancer (NSCLC) cells still largely unclear. So, the aim of this study was to reveal the regulatory mechanism of corosolic acid to NSCLC. Here, we cultured A549 and PC9 cells in increasing corosolic acid concentrations, as well as treated mice with a physiologically relevant concentration of the compound, and used metabolomics analysis and high-throughput sequencing to examine its influences on cell invasion and proliferation, chemoresistance, and metastasis. We found that corosolic acid inhibited cell invasion and proliferation in vivo and in vitro, as well as increase the chemosensitivity of both cell types to cisplatin. Furthermore, we found that corosolic acid destabilized the glutathione peroxidase 2-mediated redox system, which increased mitochondrial and liposomal oxidative stress. Corosolic acid also decreased the targeting protein for TPX2 level, which inhibited PI3K/AKT signaling and induced apoptosis. In addition, the accumulation of reactive oxygen species dissociated the CCNB1/CDK1 complex and induced G2/M cell cycle arrest. Taken collectively, the data indicate that corosolic acid reduces NSCLC cell invasion and proliferation, as well as chemoresistance, by inducing mitochondrial and liposomal oxidative stress.
format	article
author	Mingming Jin Yue Wu Yuqing Lou Xiyu Liu Yitian Dai Wenxiao Yang Congbiao Liu Gang Huang
author_facet	Mingming Jin Yue Wu Yuqing Lou Xiyu Liu Yitian Dai Wenxiao Yang Congbiao Liu Gang Huang
author_sort	Mingming Jin
title	Corosolic acid reduces A549 and PC9 cell proliferation, invasion, and chemoresistance in NSCLC via inducing mitochondrial and liposomal oxidative stress
title_short	Corosolic acid reduces A549 and PC9 cell proliferation, invasion, and chemoresistance in NSCLC via inducing mitochondrial and liposomal oxidative stress
title_full	Corosolic acid reduces A549 and PC9 cell proliferation, invasion, and chemoresistance in NSCLC via inducing mitochondrial and liposomal oxidative stress
title_fullStr	Corosolic acid reduces A549 and PC9 cell proliferation, invasion, and chemoresistance in NSCLC via inducing mitochondrial and liposomal oxidative stress
title_full_unstemmed	Corosolic acid reduces A549 and PC9 cell proliferation, invasion, and chemoresistance in NSCLC via inducing mitochondrial and liposomal oxidative stress
title_sort	corosolic acid reduces a549 and pc9 cell proliferation, invasion, and chemoresistance in nsclc via inducing mitochondrial and liposomal oxidative stress
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/50182fa5884445a1b56942f4fac6cc46
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Corosolic acid reduces A549 and PC9 cell proliferation, invasion, and chemoresistance in NSCLC via inducing mitochondrial and liposomal oxidative stress

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